关键词: 钌(Ⅱ)催化, 二苯甲酮, 肟醚, C—H键单氟烯基化, Z-选择性

Among the many members of the periodic table, fluorine stands out as an indispensable “magic element” in modern pharmaceutical and chemical industries due to its uniquely small atomic size and strong electronegativity, which endow it with distinctive physicochemical properties. Introducing a monofluoroalkene moiety into organic small molecules lays the foundation for the development of fluorinated lead compounds. At present, transition-metal-catalyzed C—H bond activation directed by directing groups has emerged as an efficient strategy for introducing monofluoroalkenes. However, as a strong directing group with a simple structure and easy installation, oxime ether directed C—H monofluoroalkenylation remains relatively underexplored. Against this backdrop, in this work, a novel Ru(II)-catalyzed Z-selective C—H monofluoroalkenylation of benzophenone oxime ether derivatives was reported. The method demonstrated excellent functional group compatibility, stereoselectivity, and regioselectivity, delivering the target products in moderate to excellent yields under mild and convenient conditions. In addition, the gram-scale reaction could be achieved well. Furthermore, the key five-membered ruthenium-cycle was successfully isolated and characterized. Its structure and role were elucidated unambiguously through single-crystal X-ray diffraction analysis and the relevant verification experiments, thereby clarifying the reaction mechanism. Accordingly, to a solution of benzophenone oxime ethers (0.2 mmol), [Ru(p-cymene)Cl₂]₂ (0.01 mmol) and Cs₂CO₃ (0.2 mmol) in dry 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP, 1.5 mL) in a 10 mL glass sealed-tube, the gem-difluorostyrenes (0.4 mmol) was added. The reaction mixture was stirred at 90 ℃ in an oil bath for 6 h. The reaction mixture was diluted with 30 mL dichloromethane (DCM), then successively washed with water and brine (15 mL each), dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under vacuum. Purification was performed by a column chromatography on silica gel (eluents: V(petroleum ether)∶V(ethyl acetate)=50∶1) to supply the desired products. Following this procedure, 34 target compounds were obtained with a yield as high as 91%.

Key words: Ru(II)-catalyzed, benzophenone, oxime ether, C—H monofluoroalkenylation, Z-selective